Design, synthesis, and biological evaluation of 1,3,6,7-tetrahydroxyxanthone derivatives as phosphoglycerate mutase 1 inhibitors

  • Bioorg Med Chem Lett. 2021 Mar 15:36:127820. doi: 10.1016/j.bmcl.2021.127820.
Kaixuan Jiang  1 ,  Biao Gao  1 ,  Jing Yu  1 ,  Lulu Jiang  2 ,  Ao Niu  1 ,  Yihe Jia  1 ,  Tao Meng  1 ,  Lu Zhou  3 ,  Jinxin Wang  4
Affiliations
  • 1. Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
  • 2. Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No. 826, Zhangheng Rd, Shanghai 201203, China.
  • 3. Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No. 826, Zhangheng Rd, Shanghai 201203, China. Electronic address: [email protected].
  • 4. Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: [email protected].
PMID: 33513389 DOI: 10.1016/j.bmcl.2021.127820
Abstract

Phosphoglycerate mutase 1 (PGAM1) is a promising target for Cancer treatment. Herein, we found that α-mangostin and γ-mangostin exhibited moderate PGAM1 inhibitory activities, with IC50 of 7.2 μM and 1.2 µM, respectively. Based on α-mangostin, a series of 1,3,6,7-tetrahydroxyxanthone derivatives were designed, synthesized and evaluated in vitro for PGAM1 inhibition. The significant structure-activity relationships (SAR) and a fresh binding mode of this kind of new compounds were also clearly described. This study provides valuable information for further optimization of PGAM1 inhibitors with 1,3,6,7-tetrahydroxyxanthone backbone or de novo design of novel inhibitor.

Keywords
1,3,6,7-Tetrahydroxyxanthone derivatives; Mangostin; PGAM1 inhibitor.